In the early 1960's (Banik, U.K., Pincus, G., and Jacques, J., 1962, 1964), first reported the implantation inhibition activities exhibited by certain A-nor-steroids as potent progesterone antagonists. In 1965, Pincus and Gordon (1965) reported that A-nor-5.alpha.-androstane derivatives, such as 2.alpha.,17.alpha.-diethyl,2.beta.-17.beta.-diol, 2.alpha.-ethynyl-2.beta., 17.beta.-diol-17.alpha.-methyl, 2.alpha.-acetyl-17.alpha.-ethynyl-17.beta.-ol and 2.alpha.-ethynyl-2.beta.,17.beta.-diol, possess antiestrogenic activity, as evidenced by their inhibition of estrogen-induced cell division in amitotic cells of cultured hamster's ascites tumor. However, neither direct evidence nor implication of anti-cancer activity was reported.
In the past two decades, A-nor-steroids have been developed exclusively as anti-fertility agents. See Li, R.L., 1986; Crabbe, P. et al., 1979; and Zhang, Y., 1987. Of the various A-nor-steroids, 2.alpha.,17.alpha.-diethynyl-A-nor-5.alpha.-androstane-2.beta.,17.beta.-di ol dipropionate (Anordrin) possesses significant anti-implantation activity in experimental animals (Ku, C.P. et al., 1975), and in clinical trials (Hu, C. et al., 1982). In clinical studies, hyperestrogenic side effect has been noted (Ku, C.P. et al., 1975). Since estrogen is known to cause certain hormonal-dependent cancers, efforts have been made to separate the estrogenic activity from its anti-fertility activity by chemical modifications based on the structure of A-nor-5.alpha.-androstane. See Crabbe, P. et al., 1979, Li, R., 1982, and Li, Y.S., 1983, supra. In spite of these extensive activities centered around improving anti-fertility, up to now it has not been recognized that A-nor-5.alpha.-androstanes, such as 2.alpha.,17.alpha.-diethynyl-A-nor-5.alpha.-androstane-2.beta.,17.beta.-di ol disuccinate and its analogs inhibit malignant cells growth.